We have examined the effects of hyperglycemia on membrane proteins and membrane function of endothelial cells, red blood cells and platelets in human and experimental diabetes mellitus. We have examined the possibility that a variety of membrane proteins can undergo the type of nonenzymatic glycosylation that is exhibited by hemoglobin and is exaggerated by the diabetic state. Nonenzymatic glycosylation is the only known direct covalent modification of proteins which reflects hyperglycemia. Direct glycosylation rates of membrane proteins have not been studied in normal or diabetic subjects. We have observed such changes in SDS PAGE purified, membrane proteins using a micro-determination technique for protein linked glucose which depends on sodium borotritide reduction of hydrolyzed sugars. The sensitivity of this technique is further heightened by the fact that, with the exception of collagen, glucose is not encountered as a normal component of mammalian glycoproteins. We have also begun to evaluate functional parameters in each of the selected cells for concommitant changes which would reflect exposure to hyperglycemia. These functional parameters include micropinocytosis in endothelial cells, membrane stability and deformability in red blood cells, platelet aggregation and rates of phagocytosis in cultured macrophages.